Oropharyngeal candidiasis (OPC), a common opportunistic infection in AIDS patients, is believed to arise from Candida albicans organisms that were apparently benignly colonizing the patient. Commensal C. albicans organisms typically colonize the GI tract and female vagina, and to some extent the oral cavity or the skin. In an immunocompromised host, commensal colonizers undergo a conversion to invasive pathogens that are capable of causing a wide spectrum of diseases. Although commensal C. albicans is thus important as the source of pathogenic organisms, little is known about the nature of commensal colonization and the factors that control it. The research proposed in this application seeks to understand C. albicans activities that are important during colonization and the effect of C. albicans colonization on host physiology. The first specific aim of the proposed research is to study the effects of C. albicans mutations on the ability of mutants to colonize. In the second specific aim, the hypothesis that colonization with C. albicans results in increased host susceptibility to bacterial infection will be tested. Because of the high incidence of OPC in AIDS patients, it is likely that AIDS patients are frequently colonized by C. albicans. In addition, studies in mice indicate the T cells are important in limiting the population size of C. albicans in the intestinal tract. Therefore, it is likely that AIDS patients are colonized to high level by C. albicans. The hypothesized increase in susceptibility to bacterial infection caused by C. albicans colonization may thus contribute to the susceptibility of AIDS patients to diarrheal disease. When a patient develops candidiasis, the organisms responsible for the infection are organisms that were previously carried in the patient's body without causing disease. Although there are many studies that have examined the events that occur during disease, few studies have focused on learning about the growth of the organism before disease arises. The goal of this research project is to understand what the organism does to colonize the host and to understand how colonization affects the health of the host with particular emphasis on its influence on the course of infection by enteric pathogens. [unreadable] [unreadable] [unreadable]